Chemical Mediators in Innate Resistance (PDF)

Chemical mediators in Innate resistance Dr. Mohamed O’haj Mohamed BSc., MSc., PhD, MHPE Associate Professor of Biochemistry & Medical Education Date: Sep 12th 2024 1  Chemical mediators in Innate Res...

Chemical mediators in Innate resistance Dr. Mohamed O’haj Mohamed BSc., MSc., PhD, MHPE Associate Professor of Biochemistry & Medical Education Date: Sep 12th 2024 1  Chemical mediators in Innate Resistance We have naturally many chemicals that can counteract microorganisms. 631 I Is Lysozyme in tear and saliva Oleic acid on the skin Gastric juice Normal bacterial flora Chemical mediators also found in blood, lymph and other body fluids Antimicrobial peptides Complement system Cytokines Acute-phase proteins Tai i 3 Chemical mediators in Innate resistance Antimicrobial peptides Low molecular weight proteins Broad espectrum antimicrobial activity Amphipathic Soluble in both aqueous and lipid environments 2 major types Cationic peptides Bacteriocins e 4 Chemical mediators in Innate resistance Antimicrobial peptides Cationic peptides Positively charged peptides Damage plasma membrane of pathogens bt a does www.yf irfi altering membrane permeability lysis Pore iem 3 main groups Cathelicidin 0 Defensins Histatin Cysteine Rich in Antifungal absent arginine and cysteine Isolated from saliva Bi J 5 Chemical mediators in Innate resistance Antimicrobial peptides Bacteriocins Peptides produced by normal bacterial flora im Lethal to related species Produced by Gram-positive and Gram-negative bacteria Colicins produced Lantibiotics by Gram-negative produced by Gram- E. coli t positive bacteria 6  Antimicrobial peptides mechanism of action s ds 7 Chemical mediators in Innate resistance Lysosomes After phagocytosis, microorganism are delivered to and fused with lysosomes ✓ Lysosomal hydrolases digest the entrapped microorganism. ✓ Optimum pH for their enzyme is 5 ✓ Their membrane is lipid monolayer Lysosomes contain polysaccharide, protein, lipid and nucleic acid hydrolytic enzymes Chemical mediators in Innate resistance Complement system Composed of >30 serum proteins Augments (or “complements”) antibody IF the antibacterial activity of Three major activities: id a Defending against bacterial infections wBridging innate and adaptive immunity i Disposing of wastes 9 Chemical mediators in Innate resistance Complement system Opsonization Process in which microbes are coated by I serum components (opsonins) Some complement proteins are opsonins Bind to microbial cells, coating them for phagocyte recognition 10 Chemical mediators in Innate resistance Complement system Complement activation im Produced in inactive forms Activated following enzymatic cleavage Must be activated in cascade fashion Three pathways of activation c Classical Lectin Alternative 11 Complement activation Classical complement pathway Usually dependent on antigen-antibody interactions Produces cleavage products that participate in opsonization, chemotaxis, and the membrane attack complex MAC 13 Complement activation Lectin complement pathway [Mannose binding lectin pathway] Macrophages produce mannose binding protein[MBP] MBP binds to mannose present in microorganism cell wall→Activates MASP 1 40361 Binds to complement receptors phagocytes → opsonization MASP=Mannose binding lectin-associated serine protease 14 Complement activation Alternate complement pathway Results in formation of membrane attack complex 15 Chemical mediators in Innate resistance Complement system Effect of Complement activation overall job of complement is to make bacteria look nice and tasty for phagocytes By: 0 1- Opsonization process = C3a attached to bacterial cell memb. to send signals to macrophages 2- Degranulation of mast cells = produce histamine 3- Chemotactic factors = Stimulate neutrophils and T-Cells & B –cells 4- Membrane attack Complex (Mac attack) = invading bacterial cell wall leading cell lysis. so Opsonization Activation of mast cells and Phagocytosis basophiles Chemotaxis Lysis Agglutination 16 Chemical mediators in Innate resistance Cytokines gSoluble proteins or glycoproteins that are released by one cell population that act as intercellular mediators or signaling molecules Source Name of cytokines Examples Leukocyte Interleukins IL-1, IL-2, IL-4 Eukaryotic cells by Interferons IFN-α, IFN-β, viral infections IFN-γ T lymphocyte Lymphokines You will be having lecture on cytokines Mononuclear Monokines phagocytes 17 Chemical mediators in Innate resistance Acute-Phase Proteins Macrophage activation by pathogen leading to cytokine release I Cytokines stimulates Liver to produce acute phase protein includes C-reactive protein (CRP), mannose- binding lectin (MBL), surfactant proteins A (SP- A) and D (Sp-D) wit can bind bacterial surfaces and act as opsonins a 18  Summary Chemical mediators are naturally present as well as produced after attack by pathogen Antimicrobial peptides exhibits broad spectrum antimicrobial activity Complements helps in opsonization, phagocytosis, lysis. Cytokines are soluble proteins or glycoproteins that are released by one cell population 19